Methanol → 2-(4-chloro-3-(hydroxymethyl)pyridin-2-yl)-7,7-dimethyl-2,3,4,6,7,8-hexahydro-1H-cyclopenta[4,5]pyrrolo[1,2-a]pyrazin-1-one

HRID 592842Notes

Reaction equation

HRID 592842 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]([N:8]2[CH2:19][CH2:18][N:17]3[C:10](=[CH:11][C:12]4[CH2:13][C:14]([CH3:21])([CH3:20])[CH2:15][C:16]=43)[C:9]2=[O:22])[C:3]=1[CH:23]=[O:24].CO.[BH4-].[Na+]>ClCCl>[Cl:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]([N:8]2[CH2:19][CH2:18][N:17]3[C:10](=[CH:11][C:12]4[CH2:13][C:14]([CH3:21])([CH3:20])[CH2:15][C:16]=43)[C:9]2=[O:22])[C:3]=1[CH2:23][OH:24]

Participants

5

Reactant 3

HCID 887MethanolHCID 4311764Sodium borohydrideHCID 768540784-chloro-2-(7,7-dimethyl-1-oxo-1,3,4,6,7,8-hexahydro-2H-cyclopenta(4,5)pyrrolo(1,2-a)pyrazin-2-yl)nicotinaldehyde

Product 1

HCID 866843692-(4-chloro-3-(hydroxymethyl)pyridin-2-yl)-7,7-dimethyl-2,3,4,6,7,8-hexahydro-1H-cyclopenta[4,5]pyrrolo[1,2-a]pyrazin-1-oneYield 77.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A 250-mL single-neck round-bottomed flask equipped with a magnetic stirrer was charged with 4-chloro-2-{4,4-dimethyl-9-oxo-1,10-diazatricyclo[6.4.0.02,6]dodeca-2(6),7-dien-10-yl}pyridine-3-carbaldehyde 108a (9.0 g, 26.1 mmol, 1.0 eq.), methanol (50 mL), dichloromethane (30 mL), and NaBH4 (5.95 g, 156.6 mmol, 5.0 eq.) at 0° C. The reaction mixture was stirred for 1 h. After the reaction was completed, the reaction was quenched with water and concentrated under reduced pressure. The residue was extracted with dichloromethane. The combined organic layer was dried over Na2SO4 and concentrated under reduced pressure. The residue was purified by silica-gel column chromatography eluting with 1:4 ethyl acetate/petroleum ether to afford 199c as a white solid (7.0 g, 77%). MS-ESI: [M+H]+ 345.9.

Workup

  1. customA 250-mL single-neck round-bottomed flask equipped with a magnetic stirrer
  2. customthe reaction was quenched with water
  3. concentrationconcentrated under reduced pressure
  4. extractionThe residue was extracted with dichloromethane
  5. dry with materialThe combined organic layer was dried over Na2SO4
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by silica-gel column chromatography
  8. washeluting with 1:4 ethyl acetate/petroleum ether

Sources & evidence

ORD record
ord-e25dd07dac5849e09382fcc6f23105d2
Source dataset
uspto-grants-2016_01
Patent number
US09238655B2

Reaction notes

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